At birth, with the initiation of ventilation there is an increase in pulmonary blood flow and a decrease in pulmonary vascular resistance. Prostaglandins probably, at least in part, mediate this ventilation induced fall in pulmonary vasular resistance and indomethacin, an inhibitor of prostaglandin synthesis, produces pulmonary hypertension in the fetus and newborn. Recent evidence suggests that PGD2 may be important in the regulation of pulmonary blood flow in the perinatal period. PGD2 specifically lowers pulmonary arterial pressure in pump perfused fetal goat lungs and in newborn lambs with hypoxic pulmonary hypertension. It produces mild pulmonary vasoconstriction in older animals. Histamine has similar effects. In some newborns, pulmonary blood flow remains low secondary to respiratory distress, meconium aspiration or sepsis. Hypoxia increases pulmonary vascular resistance and thereby reduces pulmonary blood flow further by constriction of the small pulmonary arteries. The elevation of pulmonary vascular resistance enhances right to left shunting through the foramen ovale or ductus arteriosus. Persistent pulmonary hypertension of the newborn accounts for one percent of admissions to newborn intensive care units. There is no specific treatment and the mortality approaches fifty percent. The purpose of this study is (1) to further define the role of PGD2 and histamine, possibly released from lung mast cells, in the normal fall in pulmonary vascular resistance at birth; (2) to develop a model of pulmonary hypertension with increased pulmonary artery medial smooth muscle and define the morphologic and physiologic changes; (3) to induce pulmonary hypertension by infusion of endotoxin and define the role of platelets and prostaglandins in its pathogenesis; (4) to determine whether PGD2 will lower pulmonary arterial pressure and resistance in these two models of pulmonary hypertension. If PGD2 is important in the regulation of pulmonary blood flow in the normal and abnormal perinatal pulmonary circulations then it may be useful in the treatment of newborn pulmonary hypertension.